This invention relates to novel peptides having mitogenic activity for macrophage-like cells.
It is known that thrombin has a multiplicity of effects on cells. Thus, in addition to clotting fibrinogen and enzymatically activating other factors in the plasma-clotting system, it has been reported that thrombin has mitogenic activity in a variety of fibroblast cell lines in tissue culture. See, e.g., Perdue et al., J. Biol. Chem. 256, 2767-2776 (1981). Its function as a growth stimulator for fibroblasts is intimately linked to its esterolytic activity.
Thrombin also more recently has been described to have chemotactic activity in human peripheral blood monocytes. Bar-Shavit et al., J. Cell Biol. 96, 282-285 (1983).
Attempts have been made to identify the domain or domains of thrombin which are responsible for its various biological activities. Thus, Bar-Shavit et al, Science 220, 728-730 (1983), conclude that the chemotactic activity is mediated through a specific region on the thrombin molecule that is independent of the sites required for esterolytic activity and fibrinogen recognition. The significance of the chemotactic function is that it may be an important physiological stimulator of inflammatory responses at sites of tissue injury. This chemotactic function which involves the directional locomotion of cells is to be distinguished from a mitogenic function which is a growth factor activity in cells, i.e., a factor which stimulates the division and differentiation of cells. It has been suggested heretofore that thrombin can also elicit a mitogenic effect on macrophage-like cells. Bar-Shavit et al., J. Cell. Biol. 97, 396a, Abstract 1494 (1983).